Cognition Moderates the Relationship Between Hearing and Mobility in Cognitively Normal Older Adults

Abstract Recent data has shown a consistent but modest association between hearing impairment and poor mobility; both are strongly associated with cognition. Cognitive function may moderate the relationship between hearing and mobility. We analyzed 601 cognitively normal older participants from the Baltimore Longitudinal Study of Aging who had concurrent data on cognition (attention, executive function, sensorimotor function), hearing (pure-tone average, PTA), and mobility (6-meter gait speed, 400-meter time). We performed multivariable-adjusted linear regression to test two-way interactions between each cognitive measure and PTA. There were significant PTA interactions with all cognitive measures on 400-meter time. There was a significant interaction between PTA and sensorimotor function on 6-meter gait speed. Among cognitively normal older adults, poorer hearing is more strongly associated with poor mobility in those with low cognition, especially sensorimotor function. Future studies are needed to understand how cognition may moderate the relationship of hearing impairment with mobility decline over time.


University of pittsburgh, Pittsburgh, Pennsylvania, United States
We aimed to test the effects of motor skill training (MST) on gait automaticity measured by changes in prefrontal cortex (PFC) activation during actual walking. We used data from a 12-week trial of older adults (mean age=75.5, 60.5% women) randomized to standard physical therapy and standard+MST in a 1:1 ratio. Functional near infrared spectroscopy (fNIRS) measured PFC activation during simple and dual task walking. We will apply linear mixed models to assess effects of task, time, and MST on PFC activation. We will compare the PFC activation 1) during dual task walking compared to simple walking; 2) across visits after intervention; and 3) between participants receiving MST compared to standard physical therapy. These results will demonstrate whether gait automaticity, as evidenced by PFC activation during walking, is affected by MST.
Recent data has shown a consistent but modest association between hearing impairment and poor mobility; both are strongly associated with cognition. Cognitive function may moderate the relationship between hearing and mobility. We analyzed 601 cognitively normal older participants from the Baltimore Longitudinal Study of Aging who had concurrent data on cognition (attention, executive function, sensorimotor function), hearing (pure-tone average, PTA), and mobility (6-meter gait speed, 400-meter time). We performed multivariable-adjusted linear regression to test two-way interactions between each cognitive measure and PTA. There were significant PTA interactions with all cognitive measures on 400meter time. There was a significant interaction between PTA and sensorimotor function on 6-meter gait speed. Among cognitively normal older adults, poorer hearing is more strongly associated with poor mobility in those with low cognition, especially sensorimotor function. Future studies are needed to understand how cognition may moderate the relationship of hearing impairment with mobility decline over time.

MOLECULAR RESILIENCY AND AGING Chair: Adam Salmon
Resilience is described as the ability to respond to acute forms of stress and recover to normal homeostasis. There is growing evidence that biology of resilience is entwined with the biology of aging. With increasing age, resilience decreases and is a likely contributor to increased morbidity, frailty and susceptibility to death with age. Conversely, increased resilience across numerous physiological markers of function is associated with longevity and healthy aging. The variation in resilience in populations suggests biological and molecular regulatory mechanisms that might provide insight into interventions to improve resilience, healthy aging and longevity. In this session, speakers will provide insight regarding shortterm assays of resilience in animal models that prove useful both in delineating these biological mechanisms as well as inform on potential translational models to better understand biological resilience in human populations. The sessions focus is on defining these assays and discussion of the biological relevance each resilience assay in terms of the regulation of aging. The goals of these studies range from identifying potential predictors of individual lifespan within markers of functional resilience to leveraging geroscience to define whether markers of resilience can be modified through interventions to the aging process. Moreover, better understanding of the biology of resilience could assist in defining novel interventions that improve resilience and thereby enhance longevity.

CELLULAR RESILIENCE AS A POTENTIAL PREDICTOR OF LIFESPAN Adam Salmon, University of Texas Health San Antonio, San Antonio, Texas, United States
The progressive decline of resilience during the aging process across multiple functional systems suggests basic biological mechanisms of regulation. We exploited a primary cell model to identify markers of cellular resilience or the ability of cells in culture to respond and return to homeostasis following acute challenge including metabolic, oxidative, or proteostatic stress. Using primary fibroblasts from minimally-invasive skin biopsies of genetically heterogeneous mice, we are able to determine individual cellular resilience as well as the normal lifespan and healthspan of each donor. Our studies suggest donor age and sex affect cellular resilience and that this measure of resilience can predict functional outcomes in some interventional studies. While longevity studies continue, these studies point to a potential highly important marker of healthspan and longevity as well as a model to delineate the biology of resilience in animal and translational models.

RESILIENCE AS A DETERMINANT OF HEALTHSPAN AND LIFESPAN IN MICE Nathan LeBrasseur, Mayo Clinic, Rochester, Minnesota, United States
Dynamic measures of physical resilience-the ability to resist and recover from a challenge-may be informative of biological age far prior to overt manifestations such as age-related diseases and geriatric syndromes (i.e., frailty). If true, physical resilience at younger or middle ages may be predictive of future healthspan and lifespan, and provide a unique paradigm in which interventions targeting the fundamental biology of aging can be tested. This seminar will discuss research on the development of clinically relevant measures of physical resilience in mice, including anesthesia, surgery, and cytotoxic drugs. It will further highlight how these measures compare between young, middle-aged, and older mice, and how mid-life resilience relates to later-life healthspan and even lifespan. Finally, it will provide insight into whether interventions targeting the biology of aging can modify physical resilience in mice.

ROLE OF PHYSIOLOGICAL RESILIENCE IN AGING: CHALLENGES AND OPPORTUNITIES
Derek Huffman, Albert Einstein College of Medicine, Bronx, New York, United States Lifespan and healthspan remain a cornerstone of documenting efficacy in aging research. However, it is becoming increasingly appreciated that housing rodents in conventional, unprovoked conditions, rather than exposed to the same variety of stressors normally encountered by free-living humans, has limited our understanding of how these strategies can be translated. Resilience can be defined as the ability of an organism to respond to a physical challenge or stress and return to homeostasis. Indeed, physiologic resilience is recognized to decline with age from a weakening of interactions among multiple physiologic regulatory functions. Here, we have attempted to optimize stress assays as a means of measuring physiologic resilience in mice. Our data demonstrate that these assays can readily detect age-related deficits in recovery, are amendable to geroprotector strategies, including rapamycin, while acute exposure to a stress can accelerate aging and mortality, thereby serving as a potentially useful paradigm for testing age-delaying interventions.